ObjectiveTo investigate the efficacy of ovarian tissue cryopreservation and autologous transplantation in preserving fertility and ovarian endocrine function in patients with cervical cancer. MethodsA 26-year-old patient with stage ⅡA1 cervical cancer underwent ovarian tissue harvesting and cryopreservation during cancer surgery. Following complete remission of the cancer， autologous ovarian tissue transplantation was performed. Follow-up monitoring included assessment of menopausal symptoms， hormone levels， and follicular development. ResultsSix months after transplantation， follicle-stimulating hormone levels decreased to 6.60 U/L， and estradiol levels increased from ＜10.00 ng/L to 89.00 ng/L. At 10 months after transplantation， ultrasound monitoring confirmed follicular development and physiological ovulation in the transplanted ovarian tissue. By 15 months after transplantation， follicle-stimulating hormone levels remained stable at 7.24 U/L， and estradiol levels further increased to 368.00 ng/L. Over 2 years after transplantation， the patient successfully gave birth to a healthy baby through assisted reproductive technology. ConclusionThe restoration of endocrine and ovulation functions in the transplanted cryopreserved ovarian tissue， followed by successful pregnancy， demonstrates the clinical success of ovarian tissue transplantation.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

BACKGROUND:Exercise training is an important non-drug rehabilitation method for many heart diseases,and it can also enhance the heart's tolerance to adverse stressors(such as myocardial ischemia),that is,exercise preconditioning.Granulocyte colony-stimulating factor can effectively mobilize stem cell homing and differentiation and promote the repair of damaged myocardium.However,the effect of the combination of the two treatments is not yet clear. OBJECTIVE:To explore the effect of granulocyte colony-stimulating factor supplementation combined with high-intensity intermittent exercise preconditioning on cardiac remodeling in rats with acute myocardial infarction and investigate its possible mechanism. METHODS:Totally 58 male Wistar rats were divided into sham group(n=10),model group(n=12),model drug group(n=12),model exercise group(n=12)and model combined treatment group(n=12).The myocardial infarction rat model was made by coronary artery ligation.The model exercise group and the model combined treatment group were pretreated with 8 weeks of high-intensity intermittent exercise on an electric treadmill before modeling.The model drug group and the model combined treatment group were subcutaneously injected with human recombinant granulocyte colony-stimulating factor 3 hours after modeling for 5 days(10 μg/kg per day).At 8 weeks after administration,echocardiography was used to detect heart structure and function;heart was stained with 2,3,5-triphenyltetrazolium chloride and Masson staining to obtain myocardial infarct area and collagen volume fraction,respectively.Vessel density and cell apoptosis rate were detected by immunofluorescence.Real-time fluorescent quantitative PCR was utilized to detect the mRNA expression of embryonic genes(brain natriuretic peptide,β-myosin heavy chain)and myocardial contraction regulatory factors(α-myosin heavy chain,sarcoplasmic reticulum Ca2+-ATPase).Western blot assay was used to detect the protein expression of cardiac stromal cell-derived factor 1,CXC chemokine receptor protein 4,Janus kinase 2(JAK2),signal transducer and activator of transcription 3(STAT3),Bcl2,Bax,and cleaved caspase-3. RESULTS AND CONCLUSION:(1)Compared with sham group,myocardial infarct size,collagen volume fraction,and apoptosis rate increased(P<0.05);vessel density,left ventricular fractional shortening,and left ventricular ejection fraction decreased(P<0.05);brain natriuretic peptide and β-myosin heavy chain mRNA increased(P<0.05),α-myosin heavy chain and sarcoplasmic reticulum Ca2+-ATPase mRNA and α-myosin heavy chain/β-myosin heavy chain ratio decreased(P<0.05);stromal cell-derived factor 1,CXC chemokine receptor protein 4,Bax,cleaved caspase-3 protein expression increased(P<0.05);p-JAK2,p-STAT3,and Bcl-2 protein expression decreased(P<0.05)in the model group.(2)Compared with the model group,the above indexes in the model drug and model exercise groups were significantly improved(P<0.05).Compared with the model drug and model exercise groups,the above parameters were further ameliorated(P<0.05)in the model combined treatment group.(3)The results showed that supplementation of granulocyte colony-stimulating factor or high-intensity intermittent exercise preconditioning alone can improve cardiac remodeling in rats with acute myocardial infarction,and the combined therapy has a better effect,which may be related to the induction of stem cell homing and the activation of JAK2/STAT3 signaling pathway to inhibit cardiomyocyte apoptosis.

Objective: To explore the clinical and prognostic features of lipoprotein glomerulopathy (LPG) in renal allografts. Methods: Retrospective analysis was performed for two case of LPG in renal allografts. The onset time was 6 and 9 years after living transplantation respectively. Initial symptoms included proteinuria and hypoproteinemia. Color Doppler ultrasound showed an enlarged graft size and greater parenchymal echogenicity. One patient had hyperlipemia and elevated apolipoprotein E (ApoE). Methylprednisolone pulse was offered with an early control of hyperlipidaemia and proteinuria by fenofibrate and angiotensin-converting enzyme inhibitors (ACEIs). Yet it had no effect on graft function. The definite diagnosis was made by graft biopsy. Pathological examination indicated non-homogeneous lipid deposition in glomerular capillary, glomerular sclerosis, mesangial hypercellularity and tubular atrophy. Results: During a follow-up period of 8 and 10 years post-transplantation, two cases eventually lost their grafts within 2 and 1 year after biopsy respectively. With long-term dietary control and drug therapy, regular dialysis continued and both awaited a second transplantation. Conclusions LPG is generally steroid-resistant and refractory in renal allografts. And routine biopsy is recommended for patients with a high risk of occurrence. Early controls of hyperlipemia and hypoproteinemia and other risk factors should be also properly managed.

Objective To evaluate the efficacy and safety of single bolus high dose (SD group) ATG-Fresenius induction therapy in kidney transplantation vs.multiple low dose (MD group) administration.Methods A multiple center,prospective,randomized and controlled clinical study was performed on 280 de novo renal transplant recipients from 19 centers.Patients were randomized into 2 groups as follows:SD group,a single high dose (7-9 mg/kg) of ATG-F infused as an induction agent before the vessel anastomoses;MD group,2 mg/kg of ATG-F daily administrated in postoperative 4 days.All the patients accepted maintenance immunosuppressive protocol including tacrolimus,mycophenolate and prednisone.Patients were assessed and data were collected at regular schedule clinic visits on the day 1,3,7,14,30,90,180,270 and 365.The primary end point of efficacy was therapeutic failure rate [the number of death,grafts loss and acute rejection (AR)].The event first occurred should be used in the classification of patients.The non-inferiority evaluation of the two treatment regimens was done based on treatment failure rate.The secondary end points of efficacy were the incidence of AR,delayed graft function (DGF),1-year survival rate of patients and grafts,and serum creatinine at each visiting point.The indicators for safety evaluation included hemotologic variation and incidence of adverse events.Results The therapeutic failure rate in SD group was non-inferior to the MD group (17.24％ vs.23.08％).AR was the major cause of therapeutic failure and there was similar incidence of AR between SD gronp and MD group (12.07％ vs.21.37％).There was no significant difference in the incidence of DGF between SD group and MD group (12.07％ vs.6.84％,P =0.1721).The 1-year patient's survival rate and 1-year graft survival rate in SD group and MD group showed no significant difference (96.55％ vs.98.29％,P =0.6714;94.83％ vs 98.29％,P =0.2750).The serum creatinine level showed no significant differences between two groups at each visit point.There was also no significant difference in total incidence of adverse events between the two groups.In addition,there was also no statistically significant difference in the incidence of concerned and drug-related adverse events between the two groups,including infection,hemotologic abnormality,liver or renal dysfunction,gastrointestinal disorder,etc.After ATG--F administration,peripheral blood lymphocytes in the SD and the MD group immediately decreased but nearly restored to the normal level on the postoperative day 30 and 90 respectively.No severe granulocytopenia,erythropenia or thrombocytopenia occurred in both two groups.Conclusion The efficacy and safety of single high dose of ATG-F induction are non-inferior to multiple low dose ATG-F induction,moreover,single high dose of ATG-F induction is administered more conveniently and economically.

Objective To evaluate the effect of conversion from mycophenolic acid (MPA) to mizoribine (MZR) in renal transplant recipients with gastrointestinal tract (GI) symptoms.Methods A total of 355 renal transplant recipients with GI symptoms caused by MPA administration were enrolled from April 2015 to March 2017 in 25 different renal transplant centers in China.The symptomatic improvement of GI before (baseline) and after conversion to MZR (1,2,4 weeks) was assessed by each item of GI symptoms indication.In addition,the efficacy and safety of the conversion therapy during 12 months were determined.Results Patients showed improvement in GI symptoms including diarrhea,abdominal pain,abdominal distention and stomachache after conversion to MZR 1,2,4 weeks (P＜0.05).In patients with different severity of diarrhea,conversion to MZR therapy significantly improved diarrhea (P＜0.05).During 12 months,no patient experienced clinical immune rejection.We did not observe any infections,leucopenia and other serious side effects.Conclusion MZR could markedly improve GI symptoms caused by MPA administration in renal transplant recipients.

Aim To investigate the impact of CYP3 A5 genetic polymorphism on modified releasing tacrolimus pharmacokinetics in Chinese stable renal transplant re-cipients. Methods Pharmacokinetics of once daily-ta-crolimus( tac-q. d. ) and twice daily-tacrolimus( tac-b. i. d. ) were determined by CLIA, CYP3A5 genotype was measured by PCR-RFLP. Each 10 patients receiv-ing tac-q. d. and tac-b. i. d. respectively were en-rolled, and each 5 patients receiving tac-q. d. were matched to poor metabolizer ( PM ) and extensive me-tabolizer ( EM ) group respectively according to CYP3A5 genotypes. Results AUC0~24 h for tac-q. d. was 1. 78 folds higher than AUC0~12 h for tac-b. i. d. , and dose-adjusted C0 was 40% lower for tac-q. d. than for tac-b. i. d. There were no significant differences for other parameters between the two groups; Cmax, AUC0~24 h and C0 were 1. 75, 1. 96 and 2. 49 folds higher for PM than for EM, and dose-adjusted Cmax, AUC0~24 h and C0 were 1. 80, 2. 34 and 2. 64 folds higher for PM than for EM. There were good correla-tions between AUC0~24 h and C0 for tac-q. d. Conclu-sion Conversion from tac-b. i. d. to tac-q. d. results in requirement of increased tacrolimus dose and detec-tion of CYP3A5 genotype, which is necessary for ensu-ring C0 in the range of therapeutic window.

The study aims to investigate the associations of SUMO4 polymorphisms with tacrolimus concentrations in Chinese renal transplant recipients. Blood samples and clinical data were collected from 132 renal transplant recipients with tacrolimus treatment. CYP3A5*3 genotypes were detected by PCR-RFLP, and SUMO4 (rs237024, rs237025) genotypes were detected by Sequenom® MassARRAY system. SUMO4 rs237024 and rs237025 genotypes were in complete linkage disequilibrium (D' = 1). The dose-adjusted concentration of tacrolimus in SUMO4 rs237024A-rs237025A (GA-GA +AA-AA) carriers was considerably higher than that in GG-GG carriers (P < 0.05). After stratification by CYP3A5*3 genotypes, SUMO4 rs237024A-rs237025A carriers (GA-GA+AA-AA) had a higher dose-adjusted tacrolimus concentration than that in GG carriers in CYP3A5 expresser (P < 0.05). The results illustrated that SUMO4 rs237024 and rs237025 polymorphisms were associated with tacrolimus concentrations, and the test of these genotypes may be useful for individualized medicine of tacrolimus.